Contact

Jobs

Glycan-Targeted Therapeutics

Glycans are the predominant molecule on our cell surface and form a thick and complex cover around every cell type in the animal kingdom. Attached to proteins, lipids or in a free form, glycans serve as the first contact point of cell-cell but also cell-pathogen interactions. Glycans have a structural complexity and diversity that by far exceeds other fundamental macromolecules, such as nucleic acids and proteins. This is due to their unique biosynthesis pathway that directly and indirectly involves 3-4% of our entire genome. Unlike the linear and "code dictated" synthesis of proteins from nucleic acids, the complex, branched and heterogeneous structures of glycans are formed by a network of different and sometimes competing enzymes. These unique synthesis pathways result in the immense number of different glycan structures that exceeds by orders of magnitude the number of the proteins encoded by our genome.

Viruses, bacteria, parasites, plants and fungi produce unique glycan structures which are absent from mammalian cells. Furthermore, due to altered activity of the enzymes involved in glycan biosynthesis, cancer cells often exhibit aberrant glycosylation patterns that are either absent or hardly present on the surface of healthy cells. These abnormal glycosylations are involved in all cancer aspects, from tumor proliferation, invasion and angiogenesis to metastasis.

Glycobiology in general and glycotherapy in particular were lagging behind in developing basic research tools that target specific glycan structures. This is mainly due to the great difficulties to isolate and characterize specific naturally occurring glycans. Recent developments in automated glycan assembly enable us access to glycan structures which are simply unavailable from biological sources. Using synthetic glycan microarrays we can pinpoint specific glycan structures in order to better understand protein-glycan interactions in nature. These novel insights will then contribute to the development of glycan targeted compounds for basic research, therapeutics and diagnostics purposes.